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Questions and Answers
What is the first ketone body formed during ketogenesis?
What is the first ketone body formed during ketogenesis?
Which of the following is NOT a condition associated with increased ketogenesis?
Which of the following is NOT a condition associated with increased ketogenesis?
Where does ketogenesis primarily take place in the body?
Where does ketogenesis primarily take place in the body?
What hormone is secreted during starvation to stimulate lipolysis and increase free fatty acids in the plasma?
What hormone is secreted during starvation to stimulate lipolysis and increase free fatty acids in the plasma?
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Which enzymes are essential for the liver to activate ketone bodies for their oxidation?
Which enzymes are essential for the liver to activate ketone bodies for their oxidation?
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During which metabolic state is the activity of carnitine acyl transferase-I inhibited, reducing acetyl CoA production?
During which metabolic state is the activity of carnitine acyl transferase-I inhibited, reducing acetyl CoA production?
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Which ketone body is lost in expired air and urine, leading to an acetone odor in uncontrolled diabetes mellitus patients?
Which ketone body is lost in expired air and urine, leading to an acetone odor in uncontrolled diabetes mellitus patients?
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What is the primary function of ketone bodies during prolonged fasting or starvation?
What is the primary function of ketone bodies during prolonged fasting or starvation?
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What is the primary pathway for activating acetoacetate in extrahepatic tissues?
What is the primary pathway for activating acetoacetate in extrahepatic tissues?
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Which statement best describes the process of ketolysis?
Which statement best describes the process of ketolysis?
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Under which condition does acetyl CoA shift towards ketogenesis?
Under which condition does acetyl CoA shift towards ketogenesis?
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What leads to the state of ketosis?
What leads to the state of ketosis?
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Which step is NOT part of the ketolysis process?
Which step is NOT part of the ketolysis process?
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Which of the following is a non-pathological cause of ketosis?
Which of the following is a non-pathological cause of ketosis?
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What happens to acetone during ketolysis?
What happens to acetone during ketolysis?
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How much ATP is ultimately produced from the oxidation of one molecule of β-hydroxybutyric acid?
How much ATP is ultimately produced from the oxidation of one molecule of β-hydroxybutyric acid?
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Study Notes
Ketone Bodies
- Ketone bodies are partially oxidized fatty acids.
- Three types are produced by the liver:
- Acetoacetate ("acetoacetic acid")
- β-Hydroxybutyric acid
- Acetone
- Important energy source during prolonged fasting and starvation, particularly for tissues like the brain, but not the liver (which lacks necessary enzymes).
Ketogenesis
- Definition: Synthesis of ketone bodies from active acetate derived from fatty acid oxidation and ketogenic amino acids.
- Location:
- Intracellular: Mitochondria
- Organ: Liver
- Steps:
- Acetoacetate is formed first, then the other two ketone bodies are derived from it.
- Acetoacetyl CoA formation:
- Byproducts of β-oxidation of fatty acids with even numbers.
- By the condensation of two acetyl CoA molecules.
- Conversion of acetoacetyl CoA to acetoacetate: Deacylation of acetoacetyl CoA.
- Formation of β-Hydroxybutyric acid: From acetoacetate by β-hydroxybutyric acid dehydrogenase, using NADH+H.
- Formation of acetone: Lost in expired air and urine; characteristic odor in uncontrolled diabetes.
Ketogenesis Steps Summary
- Fatty acids undergo β-oxidation; excess acetyl CoA is generated.
- Acetyl CoA produces acetoacetyl CoA.
- Acetoacetyl CoA forms acetoacetate (the initial ketone).
- Acetoacetate converts to β-hydroxybutyrate and then acetone.
Regulation of Ketogenesis
- Conditions associated with increased ketogenesis:
- Starvation and fasting
- Diabetes
- High-fat diet
- Low-carbohydrate diet
- Factors regulating ketogenesis:
- Rate of free fatty acids arriving at the liver
- Hormonal regulation
- Amount of energy in the cell
Ketogenesis Regulation After Meals
- Insulin secretion inhibits lipolysis
- Reduced free fatty acids in the plasma
- Reduced uptake of free fatty acids by the liver
- Reduced β-oxidation
- Reduced acetyl CoA precursor
- Reduced ketone body production
Ketogenesis Regulation During Starvation
- Anti-insulin hormone (glucagon) stimulates lipolysis
- Elevated free fatty acids in the plasma
- Increased uptake of free fatty acids by the liver
- Increased β-oxidation
- Increased acetyl CoA precursor
- Increased ketone body production
Ketolysis (Ketone Body Oxidation)
- Complete oxidation of ketone bodies into H₂O and CO₂.
- Location: Extrahepatic tissues (not in the liver, which lacks enzymes).
- Steps:
- Acetone is lost in urine and expired air.
- β-hydroxybutyric acid is converted into acetoacetate, with NADH+H production.
Acetoacetate Activation
- Acetoacetate activation in extrahepatic tissues occurs via two pathways.
- Major pathway: Thiophorase transfers CoA from succinyl CoA to acetoacetate, creating acetoacetyl CoA.
- Minor pathway: Acetoacetyl CoA synthetase activates acetoacetate in the presence of ATP and CoA, also creating acetoacetylCoA.
Bioenergetics of Ketolysis
- Oxidation of one β-hydroxybutyric acid molecule produces:
- 1 NADH = 2.5 ATP
- 2 Acetyl CoA = 20 ATP
- 1 ATP loss
- Net energy = 22.5 -1 = 21.5 ATP
Ketosis
- Definition: When the rate of ketogenesis exceeds the oxidative capacity of extrahepatic tissues to use ketone bodies, leading to elevated ketone levels in the blood (ketonemia) and urine (ketonuria).
Causes of Ketosis
- Pathological causes:
- Phlorhizin poisoning
- Diabetes mellitus
- Renal glucosuria
- Non-pathological causes:
- Starvation
- Carbohydrate-poor diet
- High-fat diet
- Excessive exercise
Ketoacidosis
- Definition: A type of metabolic acidosis that arises from ketosis.
- Mechanism: Increased ketone bodies (weak acids) are neutralized by blood buffers (primarily bicarbonate), decreasing blood pH (acidosis).
- Effects:
- Acidosis can cause potassium ion transfer from intracellular to extracellular fluid, leading to hyperkalemia.
- Dizziness and loss of concentration
- Severe cases may result in coma.
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Description
Explore the fascinating world of ketone bodies and their synthesis through ketogenesis. This quiz covers their types, production in the liver, and significance during fasting. Test your understanding of the metabolic pathways associated with fatty acids and energy utilization.
